EXOGENOUS BUT NOT ENDOGENOUS EBV INDUCES LYMPHOMAS IN BEIGE NUDE XID MICE CARRYING HUMAN LYMPHOID XENOGRAFTS

Epstein-Barr virus (EBV) is a latent human herpes virus that growth-transforms EBV receptor/CD21+ B cells and is associated with several high-frequency malignancies. Reactivation of latent EBV occurs in approximately 1/3 of organ graph recipients and a majority of AIDS patients; EBV-positive B lymphoproliferative lesions represent often fatal complications in organ transplantation and late-stage AIDS. Although such lymphomas can arise from endogenous virus, the high tumor risk in EBV-seronegative transplant recipients implies de novo infection, in particular virus transmission with intra-graft B lymphocytes. Since SCID mice engrafted with human lymphocytes (SCID(hum)) typically develop endogenous EBV+ (human) tumors in their graft it is difficult to study exogenous virus transmission in this model. We here demonstrate that beige/nude/xid mice engrafted with human lymphoid cells (BNX(hum)) selectively accept human B but not T cell grafts. Unexpectedly these mice fail to develop endogenous lymphomas observed in SCID(hum) mice engrafted in parallel. However, injection of as few as < 500 EBV particles produces rapidly fatal, polyclonal lymphomas in BNX(hum) animals. This virus sensitivity of BNX(hum) approaches conditions for EBV transmission with organ grafts.